A5027288590- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- CAR-T cell therapy research
- Cancer Cells and Metastasis
- Immunotherapy and Immune Responses
- Ovarian cancer diagnosis and treatment
- Cancer, Hypoxia, and Metabolism
- Monoclonal and Polyclonal Antibodies Research
- Ferroptosis and cancer prognosis
- MicroRNA in disease regulation
- Cancer, Lipids, and Metabolism
- Epigenetics and DNA Methylation
- Medical Imaging Techniques and Applications
- Chemokine receptors and signaling
- Extracellular vesicles in disease
- Inflammatory Biomarkers in Disease Prognosis
- ATP Synthase and ATPases Research
- Glycosylation and Glycoproteins Research
- Nanoplatforms for cancer theranostics
- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- Radiopharmaceutical Chemistry and Applications
- Cell Adhesion Molecules Research
- RNA Interference and Gene Delivery
- Multiple Myeloma Research and Treatments
University of Alberta
2014-2024
Helix Biopharma (Canada)
2023-2024
Western University
2012-2018
Robarts Clinical Trials
2012-2016
Max Planck Society
2006-2014
University of Freiburg
2006-2014
University of Toronto
2009-2012
Shanghai Cell Therapy Research Institute
2012
Princess Margaret Cancer Centre
2008-2011
University Health Network
2009-2011
Abstract Plasticity of neoplasia, whereby cancer cells attain stem-cell-like properties, is required for disease progression and represents a major therapeutic challenge. We report that in breast NANOG , SNAIL NODAL transcripts manifest multiple isoforms characterized by different 5’ Untranslated Regions (5’UTRs), translation subset these stimulated under hypoxia. The accumulation the corresponding proteins induces plasticity “fate-switching” toward stem cell-like phenotypes....
Multiprotein complexes (MPCs) play crucial roles in cell signaling. Two kinds of MPCs can be distinguished: (i) Constitutive, abundant MPCs--for example, multisubunit receptors or transcription factors; and (ii) signal-induced, transient, low copy number that form upon binding Src-homology 2 (SH2) domain-containing proteins to tyrosine-phosphorylated proteins. Blue native polyacrylamide gel electrophoresis (BN-PAGE) is a separation method with higher resolution than filtration sucrose...
Isolation and characterization of tumourigenic colon cancer initiating cells may help to develop novel diagnostic therapeutic procedures.We characterized a panel fourteen human carcinoma cell lines their corresponding xenografts for the surface expression potential stem markers CD133, CD24, CD44, CDCP1 CXCR4. In five nine xenografts, mRNA these was determined. Tumour growth behaviour CD133+, CD133- unsorted SW620 evaluated in vivo.All putative showed distinct patterns tumours examined. Two...
Activation of the T cell receptor (TCR) by antigen is key step in adaptive immunity.In abTCR, induces a conformational change at CD3 subunits (CD3 CC) that absolutely required for abTCR activation.Here, we demonstrate CC not induced stimulation mouse G8 or human Vg9Vd2 gdTCR.We find there fundamental difference between activation mechanisms and gdTCR map to constant regions TCRab/gd heterodimers.Enforced induction with less commonly used monoclonal anti-CD3 promoted proximal signaling but...
Ovarian carcinomas are a group of distinct diseases classified by histotypes. As histotype-specific treatment evolves, accurate classification will become critical for optimal precision medicine approaches.To uncover differences between the two most common histotypes, high-grade serous (HGSC) and endometrioid carcinoma, we performed label-free quantitative proteomics on freshly frozen tumor tissues (HGSC, n = 10; 10). Eight candidate protein biomarkers specific to carcinoma were validated...
Acidosis is an important immunosuppressive mechanism that leads to tumor growth. Therefore, we investigated the neutralization of acidity improve immunotherapy response. L-DOS47, a new targeted urease immunoconjugate designed neutralize acidity, has been well tolerated in phase I/IIa trials. L-DOS47 binds CEACAM6, cell-surface protein highly expressed gastrointestinal cancers, allowing cleave endogenous urea into two NH4+ and one CO2, thereby raising local pH. To test synergetic effect...
The γδ T cell receptor for antigen (TCR) comprises the clonotypic TCRγδ, CD3 (CD3γε and/or CD3δε), and ζζ dimers. cells do not develop in CD3γ-deficient mice, whereas human patients lacking CD3γ have abundant peripheral blood expressing high TCR levels. In an attempt to identify molecular basis these discordant phenotypes, we determined stoichiometries of mouse TCRs using blue native polyacrylamide gel electrophoresis anti-TCR–specific antibodies. isolated digitonin from primary cultured...
Breast cancers expressing human embryonic stem cell (hESC)-associated genes are more likely to progress than well-differentiated and thus associated with poor patient prognosis. Elevated proliferation evasion of growth control similarly disease progression, classical hallmarks cancer. In the current study we demonstrate that hESC-associated factor Nodal promotes breast cancer growth. Specifically, show is elevated in aggressive MDA-MB-231, MDA-MB-468 Hs578t lines, compared poorly MCF-7 T47D...
Gamma delta T cells (GDTc) lyse a variety of hematological and solid tumour in vitro vivo, are thus promising candidates for cellular immunotherapy. We have developed protocol to expand human GDTc vitro, yielding highly cytotoxic Vgamma9/Vdelta2 CD27/CD45RA double negative effector memory cells. These express CD16, CD45RO, CD56, CD95 NKG2D. Flow cytometric, clonogenic, chromium release assays confirmed their specific cytotoxicity against Ph+ cell lines vitro. generated fluorescent...
Interactions between immune and tumor cells in the microenvironment (TME) often impact patient outcome, yet remain poorly understood. In addition, effects of biophysical features such as hypoxia [low oxygen (O2)] on within TME may lead to evasion. Gamma delta T (γδTcs) naturally kill transformed are therefore under development immunotherapy for various cancers. Clinical trials have proven safety γδTc increased circulating levels correlate with improved outcome. Yet, function infiltrating...
Tumour uptake of 13N-labelled ammonia was studied by means positron emission computerised axial tomography in 46 patients with various extensive neoplastic conditions. Eleven the have been followed sequentially before, during and after radio- and/or chemotherapeutic treatment. Substantial accumulation 13NH3 (up to five times amount found comparable normal tissues) noted some cases breast cancer their metastases, as well soft tissue sarcomas, malignant neck nodes secondary head tumours, lung...
BackgroundWe systematically analyzed multiple myeloma (MM) cell lines and patient bone marrow cells for their engraftment capacity in immunodeficient mice validated the response of resulting xenografts to antimyeloma agents. Design MethodsUsing flow cytometry near infrared fluorescence in-vivo-imaging, growth kinetics MM L363 RPMI8226 were investigated with use a murine subcutaneous implant, intratibial intravenous approach NOD/SCID, NOD/SCID treated CD122 antibody IL-2Rγ(null) (NSG)....
Gamma delta T cells (γδTc) have tremendous anti-tumoral activity, thus γδTc immunotherapy is currently under development for various malignancies. We targeted breast cancer stem-like (BCSC), a rare cell population responsible patient mortality. BCSC were mostly susceptible to immunotherapy, yet some escaped. The secretome rendered hypo-responsive, and resistant expressed more PD-L1 anti-apoptotic protein MCL-1 than non-stem-like (NSC). resistance was partially overcome by dMCL1-2, an...
Abstract Despite recent progress in the understanding of γδ T cells’ roles and functions, their interaction with αβ cells still remains to be elucidated. In this study, we sought clarify what precisely endows peripheral Vδ2 + immunosuppressive function on autologous cells. We found that negatively freshly isolated do not exhibit suppressive behavior, even after stimulation IL-12/IL-18/IL-15 or sheer contact butyrophilin-3A1-expressing tumor cell lines (U251 SK-Mel-28). On other hand,...
Structural information about immune receptor complexes is important for understanding signal transduction mechanisms. We have used the Drosophila S2 cell reconstitution system identification of disulfide bonds within and between CD79a (Ig-alpha) CD79b (Ig-beta), heterodimeric transducing element B antigen (BCR). Cysteines 113 135 Ig-alpha Ig-beta, respectively, form intermolecular bridge stabilizing Ig-alpha/Ig-beta heterodimer in both cells line J558L. Furthermore, using transfected cells,...
The γδ T cell receptor for antigen (TCR) comprises the clonotypic TCRγδ, CD3 (CD3γe and/or CD3δe), and ζζ dimers. cells do not develop in CD3γ-deficient mice, whereas human patients lacking CD3γ have abundant peripheral blood expressing high TCR levels. In an attempt to identify molecular basis these discordant phenotypes, we determined stoichiometries of mouse TCRs using blue native polyacrylamide gel electrophoresis anti-TCR–specific antibodies. isolated digitonin from primary cultured...
Abstract Background Studying the stoichiometry and intracellular trafficking of T cell antigen receptor (TCR) is pivotal in understanding its mechanisms activation. The αβTCR includes antigen-binding TCRαβ heterodimer as well signal transducing CD3εγ, CD3εδ ζ 2 subunits. Although TCR-interacting molecule (TRIM) also part complex, it has not been included most reports so far. Results We used native antibody-based mobility shift (NAMOS) assay a first dimension (1D) blue (BN)-PAGE 2D...
Breast cancer is a complex and heterogeneous disease that affects about one out of every eight women. In the last decade, several advancements have been made increased our understanding breast allowed us to more accurately diagnose treat this in targeted manner. For example, gene expression profiling enabled classification cancers into four main subtypes - basal-like, HER2+ (human epidermal growth factor receptor 2-positive), luminal A B used direct use therapies such as tamoxifen or...